This is a new application for a K01 award for Dr. Milena Gianfrancesco, an epidemiologist at the University of California, San Francisco (UCSF) School of Medicine, who plans a research program focusing on understanding risk factors as they relate to rheumatic disease patient outcomes, such as adverse events. Combined with a training plan focused on computational text mining methods and advanced causal inference statistics, the goal of the current study is to use large electronic health record and national registry data that reflects real-world prescribing patterns to examine the risk of infection attributed to biologic disease-modifying anti-rheumatic drugs in individuals with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). While biologic medications have improved disease control and are associated with significant gains in patients? quality of life, several studies have demonstrated that biologic use is associated with an increased risk of serious adverse events, such as infection. How this risk differs based on a variety of patient factors, such as age, race, and ethnicity, is currently unknown, leaving clinicians with insufficient information to predict the probability of an adverse event occurring in a given patient who is prescribed a particular biologic. This proposal will utilize established local electronic health record and national registry data to examine over 80,000 individuals with RA and SLE to address three specific aims. In Aim 1, Dr. Gianfrancesco will apply and validate a text mining system to identify incident clinical and opportunistic infections from clinical notes. In Aim 2, Dr. Gianfrancesco will use the same databases to determine the longitudinal causal effect of biologics on risk of infection. In Aim 3, a risk-assessment model to predict risk of infection will be developed and validated in a rheumatology clinic. Findings from this study will further elucidate factors associated with infectious risk for individuals prescribed biologics, thereby improving their safety in the ambulatory settings. Dr. Gianfrancesco has assembled an exceptional mentorship team with expertise in computational text mining methods, advanced causal inference statistics, rheumatology and patient safety outcomes, as well as experience using national registry data to address these questions. She will have access to a rich research environment and provided support for career development through programs such as the UCSF Clinical and Translational Science Institute K-scholars program. Formal coursework and mentoring will also be supplemented with attendance at national conferences related to rheumatology, epidemiology, and informatics. Completing the proposed research and career development plan will allow Dr. Gianfrancesco to gain experience in state-of-the-art computational methods using large datasets to better understand important patient outcomes, such as serious adverse events. This mentored career development award will provide the skills, mentorship, and experience necessary to propel her to independence and enable her to lead an independent multidisciplinary research program.